Describe the molecular lesions induced in mammalian cells by hyperthermia and determine which of these lesions result in cell lethality. More specifically, differentiate between heat-induced lesions which in themselves cause cell lethality and those which radiosensitize the cells by interacting with X-ray-induced lesion. The aim is to determine the molecular basis by which heat kills and radiosensitizes mammalian cells. Specifically, why does a hyperthermic treatment reverse the order of radiosensitivity during the cell cycle, i.e., make the relatively radioresistant S phase cells more radiosensitive than the G1 cells? Secondly, if hypoxic cells are sensitized more by heat than oxygenated cells, why does this occur? Thirdly, what are the various molecular lesions associated with the different treatment protocols of combined heat and radiation therapy which cause variations in thermal radiosensitization? The general approach is to search for a correlation in variations in the number of molecular lesions and the kinetics of their repair with variations in chromosomal aberrations and cell lethality. The molecular lesions to be studied in asynchronous and synchronous Chinese hamster cells in culture are: single and double strand breaks in DNA, single stranded regions, the attachment of DNA to the nuclear membrane, and changes in chromosomal proteins associated with DNA. As an important and specific question, we hope to identify a particular type of lesion responsible for chromosomal aberrations. These are lesions which have been shown to be induced by X-rays during G1 or S but by heat only during S phase.